The objective of this research is to elucidate potential metabolic and neurochemical pathways of tetrahydroisoquinoline condensation products which might be at the basis of chronic alcoholic brain damage. Catecholamine-related tetrahydroisoquinolines and their possible oxidized metabolites are being synthesized and their metabolism studied in rat brain in vivo and in vitro. The chronic effects of these derivatives on brain monoaminergic pathways are to be investigated in rats. The interactions of the condensation products with the serotonergic system will receive emphasis. Analytical research on isoquinolines in the fluids of primates or human alcoholics under controlled intoxication conditions will be done in collaboration with other clinical investigations at institutions where these models have been developed and approved. For most analyses, high performance liquid chromatography with electrochemical and fluorescence detection and capillary gas chromatography with electron capture detection will be utilized; some radioactive tracer metabolic work in animals is proposed.